Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality throughout the developed world. In developed countries COPD is primarily related to cigarette smoking. The search for factors that define susceptibility to cigarette smoke is an important task as only 15% of smokers develop COPD. COPD also is a leading cause of morbidity and premature mortality in rural China and in 1973-5 cumulative mortality to age 65 was 16% in the worst affected areas. Female and male mortality rates in China were about equal in the mid-70s despite dramatic differences in the frequency of smoking (77% of men versus 12% of women). This may reflect the low cumulative exposure to manufactured cigarettes and may indicate the importance of other risk factors. In the 1980s the manufacture of cigarettes in China increased dramatically, and the young people of today will reach middle and old age in the next century with high cumulative exposure levels. The proposed project seeks to identify factors related to COPD risk in this population where the full effects of cigarette smoking are not yet evident. The study has access to detailed information, including pulmonary function tests and blood pressure measurements using standardized methodology, on a cohort of approximately 10,000 35-64 year old men and women residing in 69 counties in rural China and 16 counties in Taiwan. This study population offers many advantages including low cumulative pack-years exposure and complete data on many potential risk factors including age, sex, smoking, alcohol intake, childhood exposures, indoor air pollution, adult medical history, and nutritional status measured by questionnaire and biochemical markers. Three complementary subprojects are envisioned to meet the specific aims of this project. At the first stage, county-level COPD mortality data from 1986-88 and summary measures of morbidity (aggregated individual spirometry readings) will be used in ecologic analyses and examined in relation to summary measures of exposure. Next, data on individual study subjects will be used to examine the relation of a variety of factors to COPD morbidity, assessed through pulmonary function testing and a respiratory symptom questionnaire. Finally, smaller studies of individuals are planned using either nested case-control or cohort designs, to further explore the relation of biochemical markers of nutritional status to COPD morbidity.